Tuberculosis is responsible for the death of over 3.3 million people each year, which is more than any other infectious agent. The current vaccine for tuberculosis is the BCG vaccine. BCG has been proven safe and effective at protecting young children, it is relatively inexpensive to produce, and it requires only a single immunization. Unfortunately, protecting adults from pulmonary disease with the BCG vaccine has been variably efficacious. As a result, the effort to produce a novel and efficacious vaccine for tuberculosis has intensified over the last decade. In the mouse model, the combination of a TH1 stimulating adjuvant and a M. tuberculosis derived recombinant fusion construct (Corixa Corporation) has resulted in a approximately 2 log decrease in bacterial burden following an aerogenic challenge with M. tuberculosis (approaching the level seen with the BCG vaccine). This vaccine formulation has also been effective in the guinea pig and cynomolgus monkey models of tuberculosis. This application proposes to investigate the ability of a transcutaneous immunization (TCI) to deliver this vaccine formulation to mice. The effectiveness of TCI has been demonstrated in pre-clinical and clinical trials and has been shown to induce both serum and mucosal humoral responses as well as cellular immune responses. The success of this novel delivery method will be evaluated by its ability to induce the development of a TH1 immune response and to provide a significant level of protection following a low dose aerosol challenge with M. tuberculosis. If successful, the advantages of transcutaneously delivering a vaccine for tuberculosis would be the lack of a needle injection, the simplicity of administration (especially in developing countries where tuberculosis is endemic), and the potential for using a lower dose of specific antigen, which would decrease the cost of vaccination.